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Epigenetic modifications, most importantly DNA methylation events, are frequently involved in transcriptional changes in both tumor suppressor genes and oncogenes. Methylation of cytosine at CpG dinucleotides is a common feature of a higher eukaryotic genomes. DNA methylation in the promoter regions of genes is generally correlated with gene silencing. Two underlying mechanisms have been identified. First, binding of transcription factors or enhancer blocking elements, such as CTCF, may be inhibited by DNA methylation. The second and more general mechanism involves proteins that detect methylated DNA through methyl CpG-binding domains (MBDs). Four of these proteins—MBD1, MBD2, MBD3, and MeCP2—have been implicated in methylation-dependent repression of transcription. These proteins mediate recruitment of repressor complexes that include histone deacetylases (HDACs). HDACs remove acetyl groups from lysine residues of histones H3 and H4 that results in condensation of chromatin and thus limit access of transcription factors to promoter regions of genes localized nearby.

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